Immuntherapeutische Behandlung therapierefraktärer und rezidivierter akuter lymphatischer Leukämien im Kindes- und Jugendalter

Acute lymphoblastic leukemia (ALL) represents the most frequent malignant disease in childhood and adolescence and offers a good prognosis with approximately 80% survival in first remission after polychemotherapy and radiotherapy. In addition,many children with relapsed or refractory ALL will still be cured by allogeneic hematopoietic stem cell transplantation (alloHSCT).However, therapeutic options are limited with a very poor prognosis in case of another relapse after alloHSCT.Here,immunotherapy strategies offer a promising alternative to another chemotherapy or second alloHSCT, which are mainly palliative and accompanied by high morbidity and mortality. Immunotherapy strategies aim at an improvement of the graft-versus-leukemia (GvL) effect.The therapeutic GvL effect is usually associated with graft-versus-host disease (GvHD).The definition of patients subgroups with an increased risk for relapse after alloHSCT gains growing importance for immunotherapy strategies.Promising approaches for separation of GvL-effect and GvHD after donor lymphocyte infusions, e.g. T-cell suicide gene therapy, will be described. Finally, vaccination strategies for ALL exist.     

Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays.

We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray.     

Mother-to-Child Transmission of Congenital Chagas Disease,Japan

We report a patient with congenital Chagas disease in Japan. This report reemphasizes the role of neglected and emerging tropical diseases in the era of globalization. It also indicates the need for increased vigilance for detecting Chagas disease in non–disease-endemic countries.     

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.